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Knowledge and understanding of the appearance of normal bone marrow (BM) and therefore normal haematopoiesis is essential for both general pathologists and specialist haematopathologists. It is only once normal cytology and histology is understood that abnormalities can be identified and defined, leading to the accurate diagnosis of pathologies seen in the BM.
Adverse programming of adult non-communicable disease can be induced by poor maternal nutrition during pregnancy and the periconception period has been identified as a vulnerable period. In the current study, we used a mouse maternal low-protein diet fed either for the duration of pregnancy (LPD) or exclusively during the preimplantation period (Emb-LPD) with control nutrition provided thereafter and postnatally to investigate effects on fetal bone development and quality. This model has been shown previously to induce cardiometabolic and neurological disease phenotypes in offspring. Micro 3D computed tomography examination at fetal stages Embryonic day E14.5 and E17.4, reflecting early and late stages of bone formation, demonstrated LPD treatment caused increased bone formation of relative high mineral density quality in males, but not females, at E14.5, disproportionate to fetal growth, with bone quality maintained at E17.5. In contrast, Emb-LPD caused a late increase in male fetal bone growth, proportionate to fetal growth, at E17.5, affecting central and peripheral skeleton and of reduced mineral density quality relative to controls. These altered dynamics in bone growth coincide with increased placental efficiency indicating compensatory responses to dietary treatments. Overall, our data show fetal bone formation and mineral quality is dependent upon maternal nutritional protein content and is sex-specific. In particular, we find the duration and timing of poor maternal diet to be critical in the outcomes with periconceptional protein restriction leading to male offspring with increased bone growth but of poor mineral density, thereby susceptible to later disease risk.
Dietary electrolyte balance (dEB) is known to affect acid−base status and mineral metabolism, but is rarely considered in diet formulation for pigs. Yet, the use of a wide variety of local feedstuffs in Europe contributes to lowering the dEB and increasing the fibre content. Hence, mineral requirements may be modified and skeletal health affected. Therefore, the effects of a lower dEB and a higher dietary Ca level on acid−base balance and mineral status were assessed in young pigs fed a diversified diet. A total of twenty-four weaned pigs were fed a control moderate-dEB diet (C) or a diversified moderate-dEB (D), low-dEB (D-A) or low-dEB supplemented with Ca (D-CA) diet. Growth performance, venous blood gas and chemistry, urine pH, mineral balance and femur characteristics were determined. With an equivalent dEB compared with the C diet, the D diet caused an acidification of the urine and increased the excretion of P as a result of a higher dietary content of S. Low-grade metabolic acidosis occurred in piglets fed the D-A diet with changes at systemic and urine levels. A higher excretion of ammonia and P in urine was observed and some bone characteristics tended to be negatively affected. Ca supplementation partially counteracted the effects of low-grade acidosis. Urine excretion of P and ammonia was alleviated and bone characteristics improved. In conclusion, a higher Ca supply must be considered in more diversified diets to counteract the risk of evolving towards low-grade metabolic acidosis which can negatively affect bone.
Surface modification of titanium and titanium alloys is a common method to improve anchoring of bone tissue and implants in hard tissue engineering applications. In the current work, a combination of chemical and physical methods (anodization and physical vapor deposition) was used to roughen the titanium surface and deposit iron (Fe) on the surface of titanium at different thicknesses. The optimized thickness of 100 Å was selected for mechanical and biological characterization. We found that anodization increases the surface roughness of Ti from 21 ± 0 to 229 ± 9 nm, whereas Fe deposition does not change it significantly. Our results also showed that surface modification of Ti by anodization increases the proliferation of osteosarcoma cells at both time points, whereas Fe-deposited samples showed the lowest cellular activity. These results suggest that Fe-deposited Ti implants may be suitable candidates for patients with osteosarcoma, as the proliferation of malignant cells decreases in the presence of Fe.
Selective serotonin reuptake inhibitors (SSRIs) are a widely used group of antidepressants (ADs) with reported potential detrimental effects on bone mineral density (BMD) and increased fracture risk. Here, a comprehensive review of the in vitro, in vivo and clinical studies to date was carried out using the medical search engines MEDLINE (1950 to September 2010) and EMBASE (1980 to September 2010). Serotonin (5-HT) receptors have been identified on osteoclast, osteoblast and osteocyte cell lines. The effect of SSRIs on bone formation and resorption appears to be governed by the activation of a number of 5-HT receptors on osteoblasts and osteoclasts via endocrine, autocrine/paracrine and neuronal pathways. In vitro, in vivo and clinical collective data appears to indicate that SSRIs have a negative effect on bone at the therapeutic dose levels widely used for the treatment of depression in current clinical practice. Caution may therefore have to be employed with the use of SSRIs in patients at an increased risk of falls and osteoporosis. Further studies are needed in order to fully elicit the role of SSRIs in bone formation and their effects in the low oestrogen state.
Vitamin D deficiency has been commonly reported in elite athletes, but the vitamin D status of UK university athletes in different training environments remains unknown. The present study aimed to determine any seasonal changes in vitamin D status among indoor and outdoor athletes, and whether there was any relationship between vitamin D status and indices of physical performance and bone health. A group of forty-seven university athletes (indoor n 22, outdoor n 25) were tested during autumn and spring for serum vitamin D status, bone health and physical performance parameters. Blood samples were analysed for serum 25-hydroxyvitamin D (s-25(OH)D) status. Peak isometric knee extensor torque using an isokinetic dynamometer and jump height was assessed using an Optojump. Aerobic capacity was estimated using the Yo-Yo intermittent recovery test. Peripheral quantitative computed tomography scans measured radial bone mineral density. Statistical analyses were performed using appropriate parametric/non-parametric testing depending on the normality of the data. s-25(OH)D significantly fell between autumn (52·8 (sd 22·0) nmol/l) and spring (31·0 (sd 16·5) nmol/l; P < 0·001). In spring, 34 % of participants were considered to be vitamin D deficient (<25 nmol/l) according to the revised 2016 UK guidelines. These data suggest that UK university athletes are at risk of vitamin D deficiency. Thus, further research is warranted to investigate the concomitant effects of low vitamin D status on health and performance outcomes in university athletes residing at northern latitudes.
Giant cell tumor (GCT) of bone is a common benign lesion that causes significant morbidity due to the failure of modern medical and surgical treatment. Surface ultra-structures of giant cells (GCs) may help in distinguishing aggressive tumors from indolent GC lesions. This study aimed to standardize scanning electron microscopic (SEM) imaging of GC from GCT of bone. Fresh GCT collected in Dulbecco's Modified Eagle Medium was washed to remove blood, homogenized, or treated with collagenase to isolate the GCs. Mechanically homogenized and collagenase-digested GCs were imaged on SEM after commonly used drying methodologies such as air-drying, tetramethylsilane (TMS)-drying, freeze-drying, and critical point-drying (CPD) for the optimization of sample processing. The collagenase-treated samples yielded a greater number of isolated GC and showed better surface morphology in comparison to mechanical homogenization. Air-drying was associated with marked cell shrinkage, and freeze-dried samples showed severe cell damage. TMS methodology partially preserved the cell contour and surface structures, although the cell shape was distorted. GC images with optimum surface morphology including membrane folding and microvesicular structures on the surface were observed only in collagenase-treated and critical point-dried samples. Collagenase digestion and critical point/TMS-drying should be performed for optimal SEM imaging of individual GCs.
The Danube region in Central Europe was one of the areas where several cultures appeared before moving further or being defeated during the Migration Period in the middle of the first millennium AD. The Lombards, who crossed the Danube in 505 AD, settled in the “Tullnerfeld” where the Maria Ponsee graveyard was excavated in 1965–1972. From the historical evidence about the temporal and spatial migration of the Lombards, it was concluded that the graveyard was in use between 505 and 568 AD by three groups of migrants. We processed and dated a new set of 23 bones, found in the Maria Ponsee site. The determined 14C dates fit well in the expected time interval, though discrimination between the grave groups could not be obtained. The dates were added to the chronological sequence, recording the Migration Period in Central Europe. The sequence lead to a good correlation of the modelled and historical data (Amodel = 87.6%). The results show differentiations of the respective tribes in the pre-Lombardic period. However, transitions between the Lombard phases were rather ambiguous, indicating that the Lombards set up new settlements while only partially abandoning the already inhabited ones before 546 AD.
Composite materials, or at least materials that could be regarded as composites, are widespread in nature. This is, of course, a reflection of the many gains in ‘efficiency’ that can be made by integration of two or more constituents. Moreover, the development of artificial composite materials, for mechanical and/or other purposes, has benefited considerably from insights gained by examining bio-composites, and by their direct utilisation. The kingdoms of both plants (wood, grasses, straw, etc.) and animals (bone, skin, teeth, marine shells, corals, etc.) offer many examples of highly successful materials that are essentially composites. Their importance relates not only to lessons about structure–property relationships, but also to the issue of degradation and recycling. While the ‘rotting’ of wood is often regarded as its Achilles’ heel, viable recycling strategies are increasingly required for all materials (and manufactured composites are often perceived as being unsatisfactory in this respect). It is clearly not appropriate in a book of this type to provide great detail about natural materials, or indeed about recycling, but a few of the main principles and issues involved are briefly summarised here.
Three-dimensional printing (3DP) is becoming a standard manufacturing practice for a variety of biomaterials and biomedical devices. This layer-by-layer methodology provides the ability to fabricate parts from computer-aided design files without the need for part-specific tooling. Three-dimensional printed medical components have transformed the field of medicine through on-demand patient care with specialized treatment such as local, strategically timed drug delivery, and replacement of once-functioning body parts. Not only can 3DP technology provide individualized components, it also allows for advanced medical care, including surgical planning models to aid in training and provide temporary guides during surgical procedures for reinforced clinical success. Despite the advancement in 3DP technology, many challenges remain for forward progress, including sterilization concerns, reliability, and reproducibility. This article offers an overview of biomaterials and biomedical devices derived from metals, ceramics, polymers, and composites that can be three-dimensionally printed, as well as other techniques related to 3DP in medicine, including surgical planning, bioprinting, and drug delivery.
Gelatin–chitosan–based scaffolds using different bioactive nano-ceramic phase such as hydroxyapatite (HAp), beta tri calcium phosphate (β-TCP) and 58 s bioactive glass (58 s BG) were fabricated at a fixed 30 wt% of bioceramic phase content. From FTIR spectrum of the composite scaffold, a red shift in amide I and amide II bonds from 1595 to 1545 cm−1 and a new absorption peak due to electrostatic interaction between Ca2+ and COO− were observed. Average pore size in all the composite scaffolds was in the range between 100 and 300 μm, significantly smaller than the average pore size of pure gelatin–chitosan scaffold. Gelatin–chitosan-58 s BG (GCB30) scaffold exhibited the highest amount of protein absorption of 23 mg/cm2 among all the prepared scaffolds after 36 h of incubation in bovine serum albumin (BSA) solution. Mesenchymal stem cell’s (MSC’s) proliferation onto GCB30 scaffold was significantly higher as compared to other prepared scaffolds up to 7 days of cell culture. Expression of both early marker (RUNX2) and late marker (Osteocalcin) of differentiation was higher in MSCs cultured onto GCB30 scaffold as compared to other prepared scaffolds.
Increased pressure on the poultry industry by animal-rights organisations and environmentally-conscious consumers has led to the rising popularity of cage-free housing system for hens. One of the main dangers of cage-free housing systems is the possibility for laying hens to damage their keels. Keel bone fracture incidence rate ranges up to 85%, and can lead to extensive pain in any bird, and potentially be the cause of the death for a hen in a cage-free environment. It was reported that kneel bone damage observed in flocks housed in non-cage systems was 30 to 95% while in furnished cages it was 15 to 55%. The purpose of this review is to compare the prevalence of the problem found in the three main housing systems (conventional, enriched cage, and cage-free), discuss if such damage could affect the behaviour and production of laying hens, and provide potential solutions for reducing the prevalence of keel bone damage. Keel fractures can negatively affect a hen in its day-to-day life by causing pain and restricting its movements. The prevalence of keel bone damage varies considerably among the studies due to differences in the system design, genetic line, age and method for determining the keel damage, which makes difficult to compare the systems. The genetic selection, adequate nutrition and modifications in the house design have shown to be useful tools in reducing keel bone damage in laying hens.
The consumption of high-Ca, high-protein dairy foods (i.e. milk, cheese, yogurt) is advocated for bone health across the lifespan to reduce the risk of low-trauma fractures. However, to date, the anti-fracture efficacy of dairy food consumption has not been demonstrated in randomised controlled trials but inferred from cross-sectional and prospective studies. The anti-fracture efficacy of dairy food consumption is plausible, but testing this requires a robust study design to ensure outcomes are suitably answering this important public health question. The evidence of skeletal benefits of dairy food consumption is equivocal, not because it may not be efficacious but because the study design and execution are often inadequate. The key issues are compliance with dietary intervention, dropouts, sample sizes and most importantly lack of deficiency before intervention. Without careful appraisal of the design and execution of available studies, precarious interpretations of outcomes may be made from these poorly designed or executed studies, without consideration of how study design may be improved. Dairy food interventions in children are further hampered by heterogeneity in growth: in particular sex and maturity-related differences in the magnitude, timing, location and surface-specific site of bone accrual. Outcomes of studies combining children of different sexes and maturity status may be masked or exaggerated by these differences in growth, so inaccurate conclusions are drawn from results. Until these critical issues in study design are considered in future dairy food interventions, the anti-fracture efficacy of dairy food consumption may remain unknown and continue to be based on conjecture.
Tricalcium phosphate (TCP) is a promising candidate in bone and dental tissue engineering applications. Though osteoconductive, its low osteoinductivity is a major concern. Trace elements addition at low concentrations are known for their impact on not only the osteoinductivity, but also physical and mechanical properties of TCP. Copper (Cu) is known for its role in vascularization and angiogenesis in biological systems. Here, we studied the effects of Cu addition on phase composition, porosity, microstructure and in vitro interaction with osteoblast (OB) cells. Our results showed that Cu stabilized the TCP structure, while no significant effect of microstructure and porosity was found. Cu at concentrations less than 1 wt.% did not have any cytotoxic effect while decreased proliferation of OBs were observed at 1 wt.% Cu doped TCP. Addition of Cu upregulated collagen type I and vascular endothelial growth factor expression in a dose dependent manner at early time-point. Furthermore, Cu reduced inflammatory gene expression by human osteoblasts. These findings show that addition of Cu to TCP may provide a therapeutic strategy that can be applied in bone tissue engineering applications.
This work focuses on the development of a system to control the formation of bone to complement developments that have enabled potent regeneration of bony tissue. Scaffolds were fabricated with chemically modified RNA encoding for bone morphogenetic protein-9 (cmBMP9) and capped with salicylic acid (SA)-containing polymer (SAPAE). The goal was to determine if SAPAE could inhibit the formation of bone in a pilot animal study since cmBMP9 has been demonstrated to be highly effective in regenerating bone in a rat calvarial defect model. The results indicated that cmBMP9 increased bone formation (30% increase in area covered compared to control) and that SAPAE trended toward reducing the bone formation. These results suggest SAPAE could be useful as a chemical agent in reducing unwanted bone formation in implants loaded with cmBMP9.
Prostate cancer has a strong preference for metastasizing to bone which is the primary cause of prostate cancer-related morbidity and mortality. The complex nature of cancer metastasis requires the development of translational models that recapitulate a specific metastatic stage. Herein, we report the mimicking of mesenchymal to epithelial transition (MET) of prostate cancer cells using highly metastatic and a non-metastatic prostate cancer cell lines. A unique cell culture technique that we termed as ‘sequential culture’ was used to create a biomimetic bone microenvironment for metastasized prostate cancer cells by introducing bioactive factors from osteogenic induction of human mesenchymal stem cells (MSCs) within the porous 3D scaffolds. The in vitro 3D tumor model can be used as a testbed to study the interaction between prostate cancer and bone microenvironment and for the design of novel therapeutic studies.
Sintered tape-cast yttria-stabilized zirconia (YSZ) was evaluated for its elemental composition, crystal structure, and imaged with atomic force microscopy (AFM) and scanning electron microscopy (SEM). Human bone marrow stem cells (hBMSC) were cultured on the ceramic and differentiated into the osteoblast lineage; alkaline phosphatase (ALP) activity was tracked as a differentiation marker. The YSZ was composed of purely tetragonal grains with a median equivalent circular diameter of 283 nm. Zirconium, yttrium, oxygen, and adventitious carbon was detected on the substrate with no other elements in significant quantities detected. YSZ samples had an RMS roughness value of 27 nm, elastic modulus of 206 ± 14 GPa, and hardness of 14 ± 2 GPa. hBMSC were observed to attach and proliferate on the YSZ surfaces and had significantly increased ALP versus the undifferentiated control cultured on glass. This method for producing a YSZ ceramic yields a typical material of this type and supports attachment and differentiation of hBMSC; thus, making it useful as a bone implant material.
The implantation and controlled release of growth factors can enhance the proliferation and differentiation of cells that promote new bone formation at defect sites. Therefore, chitosan polymer microspheres were prepared by the water-in-oil emulsion (W/O) method and solvent freeze-drying, using glutaraldehyde as an ionic crosslinker, along with the lyophilization of solvents, to microencapsulate growth factors, preventing denaturation. The microspheres were loaded with recombinant bone morphogenetic protein 2 (Rh-BMP-2). They were spherical in shape, with a rough surface ranging in particle size from 0.4 to 1.6 μm. The yield percentage with respect to the polymer was 70% and the BMP-2 load was regulated by the initial protein dose. BMP-2 release experiments were performed for 7 days in PBS solutions at pH 4 and 7.4. The results showed that the protein release rate was only 2% lower at pH 7.4. BMP-2/chitosan microspheres were compatible with the MG-63 cell line (ATCC®CRL-1427™Homo sapiens bone osteosarcoma) and could be considered drug delivery vehicles in bone tissue engineering applications.
In this study, we have successfully grown hBN/graphene heterostructures on copper thin films using chemical vapor deposition in a single process. The first and most surprising result is that graphene grows underneath hBN and adjacent to the Cu film even though it is deposited second. This was determined from cross-sectional TEM analysis and XPS depth profiling, which chemically identified the relative positions of hBN and graphene. The effect of various growth conditions on graphene/hBN heterostructures was also studied. It was found that a pressure of 200 torr and a hydrogen flow rate of 200 sccm (∼1 H2/N2) yielded the highest quality of graphene, with full surface coverage occurring after a growth time of 120 min. The resulting graphene films were found to be approximately 6–8 layers thick. The grain size of the nanocrystalline graphene was found to be 15–50 nm varying based on growth conditions.
In this study, the bioactivity and cytocompatibility of electrospun polyamide 6 (PA6)/hydroxyapatite (HA) coating on zirconia-toughened alumina (ZTA) were investigated. Adjusting the PA6/HA ratio to 1.15 (w/w) had a significant role in achieving an appropriate fibrous coating with an average diameter of 120 ± 10 nm and surface porosity of 64.3%. The surface of bare and coated samples was hydrophilic, which promoted bone regeneration. The adhesion test of the PA6/HA mat demonstrated that a cohesive coating was formed on the ZTA via electrospinning. The in vitro bioactivity test of the PA6/HA coating in simulated body fluid (SBF) corroborated the formation of a nanostructured bonelike apatite phase. Cytocompatibility of the samples was evaluated through in vitro osteosarcoma-like cell (MG63) culture assays. The cytotoxicity study showed that the electrospun PA6/HA coating significantly improved cell attachment and spreading. The development of such bioactive, biomedical coatings opens new avenues for bone tissue engineering applications.